Elixir of Life

Human life expectancy has increased >2-fold in the developed world during the past 2 centuries, resulting in a dramatic increase in elderly population. Advanced age is associated with physiological declines that ultimately lead to incapacitation of the individual and increased predisposition to diseases. Among these, cardiovascular diseases are the leading cause of death worldwide. At first glance, aging could be interpreted as a regulation of life span emerged during the evolution of metazoans from protozoans. In fact, longevity is used as the primary criteria in many biological models of aging, and, thus, numerous studies have shown extension of life span on modification of specific conserved pathways. However, such quantitative enhancement could be considered to have a lower priority over qualitative enhancement for the human life. Therefore, alleviating the immediate consequence of aging, the physiological deterioration, is the foremost goal of aging-oriented studies in humans. In this regard, healthy life expectancy, termed healthspan, can be defined as the length of time an individual is physiologically competent and able to maintain homeostasis in response to external stress but is not necessarily equated with life span. The fact that our healthspan is not keeping pace with the increasing life expectancy results in more years spent in physiological deficiency. Thus, there is a high socioeconomic, medical and scientific interest to find strategies that confer optimal physiology, thereby extending healthspan. However, our understanding of the biology of aging with a view toward improvement of physiological competency is still limited; thus, to extend the healthspan, we still need to decipher and counteract the cellular triggers of aging. At the cellular level, aging can be considered as the malfunctioning of molecular mechanisms through time, causing aberrations such as epigenetic dysregulation, telomere attrition, and elevated levels of reactive oxygen species and toxic protein aggregates. Among these, epigenetic changes have been widely explored in the past decade. Studies on a range of models spanning from yeast to humans have shown various epigenetic changes during aging, such as formation of senescence-associated heterochromatin foci; reduction in the bulk levels of the core histones; and incorporation of noncanonical histones in addition to the changes in the post-translational histone modifications, DNA methylation pattern, and noncoding RNA profile. Altogether, these molecular aberrations hamper cellular functions, which in turn manifest as systemic physiological decline that we observe as aging at the organismal level. The physiological declines eventually result in the death of the organism once they fall below a certain threshold that sustains its life. Therefore, aging is nothing other than